Efficacy and Safety of Treatment With Alpelisib Plus Endocrine Therapy in Patients With HR+, HER2-negative aBC, With PIK3CA Mutations, Whose Disease Has Progressed on or After CDK 4/6 Treatment With an Aromatase Inhibitor (AI) or Fulvestrant

Overview

About this study

Efficacy and safety of treatment with alpelisib plus endocrine therapy in patients with HR+, HER2-negative aBC, with PIK3CA mutations, whose disease has progressed on or after CDK 4/6 treatment with an aromatase inhibitor (AI) or fulvestrant

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. If you need assistance understanding the eligibility criteria, please contact the study team.

Inclusion Criteria:

  • Written informed consent must be obtained prior to any screening procedures.
  • Patient is an adult male or female ≥ 18 years old at the time of consent and has signed informed consent (ICF) before any trial related activities and according to local guidelines.
  • Males or females with advanced (locoregionally recurrent or metastatic) breast cancer not amenable to curative therapy.
  • Patient has a histologically and/or cytologically confirmed diagnosis of ER+ and/or PgR+ breast cancer by local laboratory.
  • Patient has a confirmed, HER2-negative aBC. HER2-negative defined as a negative in situ hybridization test or an immunohistochemistry (IHC) status of 0, 1+ or 2+. If IHC is 2+, a negative in situ hybridization (FISH, CISH, or SISH) test is required by local laboratory testing.
  • Patient has PIK3CA mutation confirmed by a Novartis designated laboratory, in which adequate formalin-fixed paraffin-embedded tissue sections with >10% tumor tissue must be provided. It is recommended to provide a tumor sample collected after the most recent progression or recurrence, or
  • Patient has a pathology report confirming PIK3CA mutant status by a certified laboratory using a validated PIK3CA mutation assay (either from tissue or blood). It is also mandatory to provide a tumor sample (either archival or newly obtained) for PIK3CA mutation confirmation by a Novartis designated laboratory. It is recommended the tumor sample is collected after the most recent progression or recurrence.
  • In case of women, both premenopausal and postmenopausal patients are allowed to be included in this study; menopausal status is relevant for the requirement of goserelin or leuprolide to be used concomitantly with alpelisib in combination with fulvestrant or letrozole.
    • Patient is postmenopausal woman defined as either:
      • Prior bilateral oophorectomy; or
      • Age ≥60; or
      • Age <60 and amenorrhea for 12 or more months (in the absence of chemotherapy, tamoxifen, toremifene, or ovarian suppression) and FSH and/or estradiol in the postmenopausal range per local normal range.
      • If patient is taking tamoxifen or toremifene and age <60, then FSH and plasma estradiol levels should be in post-menopausal range per local normal range.
        • Note: For women using therapy-induced amenorrhea other than ovarian radiation, goserelin or leuprolide, serial measurements (per local guidelines) of FSH and/or estradiol are needed to ensure menopausal status.
    • Patient is premenopausal defined as either:
      •  Patient had last menstrual period within the last 12 months; or
      •  If on tamoxifen or toremifene with in the past 14 days, plasma estradiol and FSH must be in the premenopausal range per local normal range; or
      •  In case of therapy induced amenorrhea, plasma estradiol and/or FSH must be in the premenopausal range per local normal range.
        • Note: Throughout this document, peri-menopausal and pre-menopausal status is grouped together and referred as “Premenopausal."
  • Patients must have:
    • Documented evidence of tumor progression on or after CDK 4/ 6 inhibitor combination treatment; CDK 4/6 inhibitor must be the last treatment regimen prior to study entry;
    • No more than two (2) prior anti-cancer therapies for aBC. Each unique regimen; or
    • ‘Line’ is defined as a single or combination of medications given for a new relapse/recurrence. This may include systemic endocrine therapy (ET) agents, where a single agent ET is considered a line of therapy. If the change to a different ET was due to progression this would be considered the 2nd line; hence that 2nd line of ET must be in combination with a CDK 4/6 inhibitor to be allowed.
    • Received no more than one prior regimen of chemotherapy for the treatment of advanced/metastatic disease is permitted.
      • Note: Patients who received chemotherapy in (neo) adjuvant therapy for breast cancer are eligible.
    • Recovered to grade 1 or better from any adverse events (except alopecia or other toxicities not considered a safety risk for the patient at investigator’s discretion) related to previous anti-cancer therapy prior to study entry.
    • For male patients, prior AI treatment is not required.
  • Patients must have either:
    • Measurable disease, i.e. at least one measurable lesion as per RECIST v1.1 criteria.  (Tumor lesions previously irradiated or subjected to other locoregional therapy will only be considered measurable if disease progression at the treated site after completion of therapy is clearly documented); or
    • If no measurable disease is present, then at least one predominantly lytic bone lesion must be present (Patients with no measurable disease and only one predominantly lytic bone lesion that has been previously irradiated are eligible if there is documented evidence of disease progression of the bone lesion after irradiation).
  • Patient has adequate bone marrow and coagulation function as shown by the following laboratory values:
    • Absolute Neutrophil Count (ANC) ≥ 1.5 x 109/L;
    • Platelets ≥ 100 x 109/L (For patients with lesions involving the bone marrow, platelet count ≥ 75 x 109/L may be acceptable);
    • Hemoglobin ≥ 9.0 g/dL;
    • INR ≤ 1.5 (INR ≤ 2.0 will be allowed for those patients treated with vitamin K antagonist).
  • Patient has adequate liver function as shown by:
    • In absence of liver metastases, serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN or ≤ 5 x upper limit of normal (ULN) if hepatic metastases are present;
    • Total serum bilirubin ≤ ULN (except for patients with Gilbert’s syndrome who may only be included if the total bilirubin is ≤3.0 × ULN or direct bilirubin ≤1.5 × ULN.
  • Patient has adequate renal function:
    • Serum creatinine ≤ 1.5 x ULN or creatinine clearance ≥ 35 ml/min using Cockcroft-Fault formula.
  • Patient has fasting plasma glucose (FPG) ≤140 mg/dL (7.7 mmol/L) and glycosylated hemoglobin (HbA1c) ≤ 6.4% (both criteria have to be met).
  • *For patients with FPG ≥ 100 mg/dL and/or HbA1c ≥5.7% (i.e. threshold for pre-diabetes) at screening, recommend lifestyle changes according to ADA guidelines, i.e. dietary advice (e.g. small frequent meals, low carbohydrate content, high fiber, balancing carbohydrate intake over the course of the day, three small meals and 2 small snacks rather than one large meal) and exercise. A consultation with a diabetologist is highly recommended.
  • Patient has potassium, magnesium and calcium (corrected for albumin), within normal limits (either by central or local lab), or ≤ Grade 1 severity according to NCI-CTCAE v4.03 if judged clinically not significant by the investigator, or correctable with supplements before entry of study; re-screen is allowed.
  • Fasting serum amylase ≤ 2 × ULN.
  • Fasting serum lipase ≤ULN.
  • Patient has ECOG (Eastern Cooperative Oncology Group) Performance Status ≤2.

Exclusion Criteria:

  • Patient has known hypersensitivity to alpelisib, fulvestrant or letrozole.
  • Patient has received prior treatment with any PI3K inhibitors.
  • Patient with an established diagnosis of diabetes mellitus type I or uncontrolled type II.
  • Patient has a concurrent malignancy or malignancy within 3 years of study screening period, with the exception of adequately treated, basal or squamous cell carcinoma, non-melanoma skin cancer or curatively resected cervical cancer.
  • Patient has received radiotherapy ≤ 4 weeks or limited field radiation for palliation ≤ 2 weeks prior to enrollment, and who has not recovered to grade 1 or better from related side effects of such therapy.
  • History of acute pancreatitis within 1 year of screening or past medical history of pancreatitis.
  • Patients with central nervous system (CNS) involvement unless they meet ALL of the following criteria:
    • At least 4 weeks from prior therapy completion (including radiation and/or surgery) to starting the study treatment;
    • Clinically stable CNS tumor at the time of screening untreated or without evidence of progressions for at least 4 weeks after treatment as determined by clinical examination and brain imaging (MRI or CT) during screening period and stable low dose of steroids for 2 weeks prior to initiating study treatment.
  • Patient with severe liver impairment (Child Pugh score B/C).
  • Patient has impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of the study drugs.
  • Patient has documented pneumonitis which is active and requiring treatment.
  • Patient has a history of Stevens-Johnson-Syndrome (SJS) or Toxic Epidermal Necroloysis (TEN).
  • Patient is concurrently using other anti-cancer therapy. All anti-cancer therapy must be discontinued prior to day one of study treatment.

Participating Mayo Clinic locations

Study statuses change often. Please contact us for help.

Mayo Clinic Location Status Contact

Rochester, Minn.

Mayo Clinic principal investigator

Donald Northfelt, M.D.

Contact us for the latest status

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

Scottsdale/Phoenix, Ariz.

Mayo Clinic principal investigator

Donald Northfelt, M.D.

Open for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

Jacksonville, Fla.

Mayo Clinic principal investigator

Donald Northfelt, M.D.

Contact us for the latest status

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

More information

Publications

Publications are currently not available

Study Results Summary

Not yet available

Supplemental Study Information

Not yet available

.
CLS-20450020

Mayo Clinic Footer